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Disclosures: Agrawal, Alberts, Miller and Snaman report no relevant financial disclosures.
December 23, 2020
12 min read

Pediatric cancer pain management requires balancing function with comfort

Disclosures: Agrawal, Alberts, Miller and Snaman report no relevant financial disclosures.
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For many people living with cancer and undergoing its various treatments, some degree of pain is inevitable, and children are no exception.

However, unlike adults, young children often are unable to clearly articulate the nature and severity of their pain.

Children with cancer often have “multilayered” pain, according to Anurag K. Agrawal, MD.
Children with cancer often have “multilayered” pain, according to Anurag K. Agrawal, MD. “It’s not only due to the organic symptoms of the cancer or the side effects of treatment, but also is very much layered on top of psychological factors like anxiety and depression, as well as insomnia and poor quality of life,” he said.
Source: Kelli Hemmingsen.

“At different ages, children have different abilities to express their symptoms and localize their pain,” Tamara P. Miller, MD, MSCE, pediatric hematologist/oncologist in the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta and assistant professor in the department of pediatrics at Emory University School of Medicine, said in an interview with HemOnc Today. “That’s just based on normal childhood development. A 2-year-old is not going to be able to convey this information the way an older child or adult could.”

These communication challenges often can be overcome in the hospital environment. But, when these children are discharged and resume their everyday lives, clinicians — and even parents — can easily become disconnected from a child’s experience of pain.

“In the inpatient setting, children are our captive audience, and we do a better job there of assessing and managing their pain with multimodal therapies,” Anurag K. Agrawal, MD, associate professor in the department of pediatrics and division of hematology/oncology and bone marrow transplant at University of California, San Francisco Benioff Children’s Hospital Oakland, said in an interview with HemOnc Today.

“But sometimes when they go out into the world, when they’re done with treatment or even on treatment in the outpatient setting, I worry that a lot of kids might have symptoms that either go undiagnosed or are not perceived by family members to be as great as they are,” Agrawal added.

HemOnc Today spoke with pediatric hematologists, oncologists and psychologists about common types of pain children with cancer experience, how challenges associated with self-reports and parental reporting complicate pain assessment, the role of opioids in managing pain in this population, and how the goals of pain management change at the end of life.

Sources, types of pain

Children with cancer experience various types of pain, often based on the type of cancer involved.

In many cases, initial reporting of pain is what leads to a cancer workup and ultimate diagnosis among children.

According to a study by Ljungman and colleagues, 49% of children experienced cancer-related pain at the time of diagnosis. This pain was often intense at the start of treatment.

As leukemia and brain tumor are the most prevalent pediatric cancers, pain associated with these cancers is a common presentation, according to Jennifer M. Snaman, MD, attending physician in the cancer and blood disorders center at Boston Children’s Hospital and assistant professor of pediatrics at Harvard Medical School.

Jennifer M. Snaman, MD
Jennifer M. Snaman

“Many children with leukemia present with bony pain from the beginning; that’s a pain that comes over days or weeks,” Snaman said. “It is similar with brain tumors and solid tumors. Often, these children present with pain that is much more acute and leads us to the diagnosis.”

Acute pain that leads to a cancer diagnosis can be alleviated greatly by treating the disease, although additional pain control may be required, Snaman said.

“We manage the pain by treating the underlying cause of it,” she said. “However, many of the treatments we use result in more acute pain. We manage mucositis and significant colitis pain with multimodal therapies, including opioids. These are usually of shorter duration and resolve over time.”

More fixed types of pain could include the nociceptive pain of a bony metastatic lesion or inflammation around the nerve root, Snaman said. Children might also have visceral pain associated with metastatic lesions to other sites.

“Children may have chronic pain associated with a limb sparing or an amputation, or chronic, neuropathic pain associated with other treatments we give,” she said.

Agrawal maintained that for children, the experience of chronic pain is often more complicated and less straightforwardly related to the cancer or its treatment.

“Our patients have very multilayered pain. It’s not only due to the organic symptoms of the cancer or the side effects of treatment, but also is very much layered on top of psychological factors like anxiety and depression, as well as insomnia and poor quality of life,” he said. “All of those things really exacerbate their expression of pain and nausea, as well as other common symptoms that can sometimes manifest.

“We definitely see that in the acute settings, the trauma that children experience ends up leading to very chronic symptoms that can be very difficult to manage by the primary oncologist,” Agrawal added.

Self-reporting challenges

The challenges implicit in children’s ability to self-report pain can not only interfere with clinical practice but also may be confounders in clinical trials.

“One of the biggest challenges is that there is a different ability to assess or express pain depending upon the age of the child,” Miller said. “Also — and this is true with adults or children — there are different levels of tolerance for pain. Some children might play right through it, and others may be more affected by it.”

Pain is a very subjective experience and individual to the person experiencing it, according to Nicole M. Alberts, PhD, associate professor in the department of psychology at the Centre for Clinical Research in Health of Concordia University.

“For example, two patients might receive the same painful needle, but one might rate the pain as a seven out of 10 while the other one rates it at a two,” she told HemOnc Today. “Different biological, social and psychological factors influence this experience of pain.”

Additionally, Miller said, clinical trials often use functional measures of pain that might not be applied as accurately to a pediatric population.

Tamara P. Miller, MD, MSCE
Tamara P. Miller

“The definition of pain or reporting of adverse events in the NCI’s Common Terminology Criteria for Adverse Events relates to what people are able to do and how much the pain affects them on a daily basis,” Miller said. “That can be extremely challenging when assessing small children who might not know how to perform some normal activities of daily living, such as buttoning their shirts, for example. So, it’s unclear if the pain in their hands is affecting their ability to perform routine tasks or if they just can’t do that task yet.”

To overcome these challenges, researchers have developed pain assessment tools specifically for children.

Faces pain scales are reliable and valid measures of pain intensity among children aged 4 to 12 years, as well as older children, according to Alberts.

“Faces pain scales and other self-report measurement tools can be used to accurately assess pain in children,” she said. “And most children aged 4 years and older can provide meaningful self-report of pain when developmentally appropriate measures are used.”

Agrawal also cited the Adolescent Pediatric Pain Tool, a multidimensional system that evaluates pain location, intensity and quality. It is used for children and adolescents in clinical practice, as well as in research.

With these tools, researchers have learned a great deal about how to determine pain in children, Agrawal said.

“We’ve done a much better job of understanding the multimodal, multilayered nature of pain in children and how to assess it,” he said. “We have improved in our assessments of how they would describe their pain and where the pain is.”

Pain management-focused electronic health records offer another approach to assessing and monitoring pediatric cancer pain. Some of these EHR systems have customizable software that places an emphasis on a patient’s pain score and needs.

Although Alberts acknowledged the potential of such systems to improve symptom collection, she noted that with children, a more hands-on approach might be more beneficial.

“Depending on the hospital, some institutions are further ahead with the [pain management EHR] but, in general, we’re moving more toward integration of patient-reported outcomes,” she said. “Use of self-report measures for pain and other symptoms is something we have done for a long time within the field of psychology, and now there’s a push toward it in several areas of medicine. We’re moving away from relying on measures such as a verbal report noted in the chart by nurses and instead are working on being able to have children and parents complete self-report measures via a tablet or other device. The goal is to directly integrate that data with the medical record quickly and easily.”

The perspective of parents

As the closest adults to the child with cancer, parents have the potential to be an excellent resource for information about a child’s pain.

“Parents are so important, so we’ll often get these pain measures from parents, as well,” Alberts said. “We’re still administering measures that are valid and reliable for kids, but we often supplement them with parent-report measures. This is particularly important in chronic pain research and in considering how pain is interfering with a child’s life.”

However, a child’s assessment of their pain is not necessarily aligned with their parents’ perceptions. A 2016 study published in Japanese Journal of Clinical Oncology showed a tendency among parents of both children with cancer and those with musculoskeletal conditions to underestimate the pain their children experienced, particularly acute pain.

“There are some studies that show that parents’ perception of the patient’s pain and that of the young child can often be quite different,” Agrawal said. “Their perceptions are actually sometimes less than what the patient is experiencing.”

In the study by Ljungman and colleagues, researchers also found that over the course of their children’s cancer treatments, parents increasingly considered themselves to be more reliable arbiters of their child’s pain than the child’s health care providers.

Snaman said asking a child questions about their pain can help clarify the situation for parents, as well.

“We might ask them, ‘Is it tingling? Does it feel like pins and needles, or is it sharp or stabbing?’” she said. “We really try to allow them to describe it as best they can. We explain to them that we need to know what type of pain it is so we can find the best way to treat it. We’re telling this to the child, but really, we’re telling that to the parents, because they might have some hesitation about using certain medications (ie, opioids) to manage the pain.”

Pain management options

How pain is treated among children is based on a variety of factors, including whether the pain is acute or chronic and what types of treatment the child is receiving.

For some types of pain, treatment may include opioids. Although these drugs have drawn scrutiny amid the national opioid epidemic, they continue to play a role in cancer pain management for adults and children.

“There are many patients, especially in the acute pain setting, who require opioids,” Agrawal said. “For patients with chronic pain, we have really tried to move away from opioid interventions because we’ve found that they’ll often mask the patient’s symptoms without addressing the underlying issues.”

Snaman added that for patients receiving upfront immunosuppressive chemotherapy, other types of pain medication may not be appropriate.

“We try to avoid nonsteroidal anti-inflammatory medications for these patients because of the concerns around bleeding,” she said. “So, that takes away a good drug for managing both pain and inflammation.”

Similarly, Snaman said oncologists worry that acetaminophen can mask a fever, which could be a sign of a serious infection. For this reason, Tylenol and other acetaminophen products are best avoided.

“We therefore often use opioids as first-line treatment,” she said. “If we had a toddler who was being treated for cancer, was immunosuppressed and had teething pain or pain from mucositis, we would actually give morphine for that, because we’d be worried about any of those other medications.”

For a more chronic pain situation in that same child, Snaman said she might consider a different approach.

“If that child were receiving vincristine and experiencing a lot of neuropathic pain and irritability, we’d want to empirically start a medicine like gabapentin,” she said.

There also are a variety of situations when clinicians may use coanalgesics, such as tricyclic antidepressants, anticonvulsants or anti-inflammatory medications (nonsteroidals, steroids, etc), Snaman added.

“These situations include incomplete pain control with front-line medications, avoidance of side effects that may be associated with higher doses of analgesia (ie, opioids), and management of complex or mixed pain,” she said.

Agrawal — who said he might consider opioids for acute situations such as chemotherapy-associated mucositis or mouth sores, following bone marrow transplant, or for acute pain after a surgical procedure — emphasized that he might avoid these drugs chronically for a patient with osteosarcoma and limb salvage or amputation.

“A patient could have phantom limb pain after amputation and neuropathic pain after limb savage that could last for many, many years, and opioids are not going to be the answer for long-term pain,” he said.

However, the decision-making process around opioids cannot be cleanly divided into “acute vs. chronic” categories, Agrawal said. For example, when acute pain morphs into acute-on-chronic pain, especially in the case of sickle cell disease, opioids may be appropriate, he said.

“There is definitely a reluctance by some providers to continue with opioids in that situation,” he said. “So, that is something that we really need to explain to ED providers, residents, etc — opioids are still the mainstay of treatment, especially when it’s an acute-on-chronic situation. It becomes a very nuanced question.”

Snaman added that often, families of pediatric patients with cancer may have major concerns about the use of opioids by their children.

“It requires a lot of education for not just the parents, but the wider family and community, as well — everyone hears ‘opioids’ and freaks out,” she said. “We also have to use a lot of safeguards to manage that.”

When there appears to be a need for a longer-term course of opioids for a child, Snaman said she utilizes “opioid contracts” or “opioid-use agreements” for the family of the child.

“These say, ‘We’ll provide this medication, but here’s what you need to do in return,’” she said. “We do that with every family that receives a prescription for a longer course of opioids or long-acting opioids. It helps to normalize the process.”

Agrawal said another valuable aspect of his long-term pain management approach is that it includes nonpharmacologic therapies, such as massage, acutherapy, biofeedback, hypnosis and more. He said these approaches are a good way to manage long-term pain and distress.

“Overall, as a group, we are recognizing some of these long-term effects and how pain and psychological concerns can all manifest,” he said. “We are doing a better job of assessing these symptoms.”

Alberts also emphasized the importance and role of psychologists within the pain team.

“Given the strong role of psychological factors in children’s experience of acute and chronic pain, a multidisciplinary approach — including the delivery of nonpharmacologic treatments such as cognitive behavior therapy, distraction and relaxation techniques, and hypnosis by a psychologist — is vital,” she said.

End-of-life pain: A shifting of goals

As a child reaches the end stages of advanced cancer, many of the pain concerns and goals associated with curative treatment may change.

Snaman, who is both an oncologist and a palliative care physician, said the key to end-of-life pain management is to layer on different medications with different mechanisms of action while also engaging the child in nonpharmacologic mind-body approaches.

“It’s multimodal, and we try to layer these drugs in a stepwise fashion, which may be harder in very advanced disease, as some children may not be able to swallow or don’t have enteral access,” she said. “Then, we really need to think about what medications we can give based on the route of administration available. If desired by the patient and family, we can usually mange all of this at home, whether with IV or oral medications. We try to use medications that treat multiple symptoms or use the side effects of one medication (sleepiness) to help with another symptom (insomnia).”

Snaman said for patients at the end of life, the goal is to optimize function as much as possible while minimizing pain and discomfort.

“We ask patients and families, ‘What is the acceptable level of pain or discomfort that will allow you/your child to be engaged with life and do what they want to do?’” she said. “We also have to recognize that in some cases, in order to effectively manage severe pain in advanced cancer, we may have the side effect of the child being less interactive.”

Snaman said this requires close monitoring of the patient and explaining the situation to them and their family.

“Some older kids may say they don’t want to feel loopy and they would rather be in some degree of pain,” she said. “We can usually find a good balance.”

Agrawal said at his institution, managing end-of-life pain is usually a multidisciplinary effort in which various specialists collaborate and coordinate care.

“Most pediatric oncology centers use a team effort between pediatric oncology, palliative care and pain management,” he said. “Those services all work together, along with our integrative medicine service. We use a combination of pharmacologic and nonpharmacologic approaches. The main difference is that, on the inpatient unit, there really is no maximum for medications such as opioids.”

He said his team uses opioids for symptoms that can occur at the end of life, including morphine and benzodiazepines for air hunger, as well as the barbiturate phenobarbital for terminal restlessness.

Another opioid Agrawal said is useful for terminal situations is methadone.

“Methadone is a great drug that is probably underutilized for chronic pain, as well as for end-of-life pain,” he said. “It can prolong the patient’s quality of life and prolong their time out of the hospital.”

Agrawal emphasized the need for oncologists to become more familiar with the nature and management of chronic pain.

“That’s not something we learn a lot about in our training,” he said. “What I’ve learned is that you really need a specialized team, a multimodal approach and time to manage these patients. I’ve grown to appreciate the benefit of the various providers — the music therapists, the art therapists, the massage therapists. All of these people have such important roles on the team.” – by Jennifer Byrne


Matziou V, et al. Jpn J Clin Oncol. 2016;doi:10.1093/jjco/hyw074.

Ljungman G, et al. Pediat Hematol Oncol. 2000;doi:10.1080/088800100276389.

For more information:

Anurag K. Agrawal, MD, can be reached at UCSF Benioff Children’s Hospital Oakland, 747 52nd St., Oakland, CA 94609; email: anurag.agrawal@ucsf.edu.

Nicole M. Alberts, PhD, can be reached at Concordia University, 7141 Sherbrooke St. West, Montreal, QC H4B 1R6; email: nicole.alberts@concordia.ca.

Tamara P. Miller, MD, MSCE, can be reached at Emory University, 1365-C Clifton Road NE, Atlanta, GA 30322; email: tamara.miller@emory.edu.

Jennifer M. Snaman, MD, can be reached at Boston Children’s Hospital, 300 Longwood Ave., Boston, MA 02115; email: jennifer_snaman@dfci.harvard.edu.